Important Safety Information for Orenitram

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

Abrupt discontinuation or sudden large reductions in dosage of Orenitram may result in worsening of PAH symptoms

Orenitram inhibits platelet aggregation and increases the risk of bleeding

The Orenitram tablet shell does not dissolve. In patients with diverticulosis, Orenitram tablets can lodge in a diverticulum

DRUG INTERACTIONS / SPECIFIC POPULATIONS

Concomitant administration of Orenitram with diuretics, antihypertensive agents, or other vasodilators increases the risk of symptomatic hypotension

Orenitram inhibits platelet aggregation; there is an increased risk of bleeding, particularly among patients receiving anticoagulants

Co-administration of Orenitram and the CYP2C8 enzyme inhibitor gemfibrozil increases exposure to treprostinil; therefore, Orenitram dosage reduction may be necessary in these patients

Pregnancy Category C. Animal reproductive studies with Orenitram have shown an adverse effect on the fetus. There are no adequate and well-controlled studies in humans

It is not known whether treprostinil is excreted in human milk or absorbed systemically after ingestion. Because many drugs are excreted in human milk, choose Orenitram or breastfeeding

Safety and effectiveness in patients under 18 years of age have not been established

There is a marked increase in the systemic exposure to treprostinil in hepatically impaired patients

ADVERSE REACTIONS

In the 12-week placebo-controlled monotherapy study, adverse reactions that occurred at rates at least 5% higher on Orenitram than on placebo included headache, diarrhea, nausea, flushing, pain in jaw, pain in extremity, hypokalemia, and abdominal discomfort

Indication

Orenitram is a prostacyclin vasodilator indicated for treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity.

The study that established effectiveness included predominately patients with WHO functional class II-III symptoms and etiologies of idiopathic or heritable PAH (75%) or PAH associated with connective tissue disease (19%). When used as the sole vasodilator, the effect of Orenitram on exercise is about 10% of the deficit, and the effect, if any, on a background of another vasodilator is probably less than this.

Important Safety Information for Remodulin

WARNINGS AND PRECAUTIONS

Chronic intravenous (IV) infusions of Remodulin are delivered using an indwelling central venous catheter. This route is associated with the risk of blood stream infections (BSI) and sepsis, which may be fatal. Therefore, continuous subcutaneous (SC) infusion is the preferred mode of administration

Avoid abrupt withdrawal or sudden large reductions in dosage of Remodulin, which may result in worsening of PAH symptoms

Titrate slowly in patients with hepatic or renal insufficiency because such patients will likely be exposed to greater systemic concentrations relative to patients with normal hepatic or renal function

Remodulin dosage adjustment may be necessary if inhibitors or inducers of CYP2C8 are added or withdrawn. Co-administration of Remodulin with a CYP2C8 inhibitor increases exposure to treprostinil, or with an inducer, decreases exposure to treprostinil

DRUG INTERACTIONS/SPECIFIC POPULATIONS

Remodulin is a potent pulmonary and systemic vasodilator. Concomitant administration of Remodulin with blood pressure lowering agents, such as diuretics, antihypertensive agents, or other vasodilators, may increase the risk of symptomatic hypotension

Since Remodulin inhibits platelet aggregation, there may be an increased risk of bleeding, particularly among patients receiving anticoagulants

Safety and effectiveness of Remodulin in pediatric patients have not been established. It is unknown if geriatric patients respond differently than younger patients. Caution should be used when selecting a dose for geriatric patients

There are no adequate and well-controlled studies with Remodulin in pregnant women. It is not known whether treprostinil is excreted in human milk

ADVERSE REACTIONS

In clinical studies of SC Remodulin infusion, the most common adverse events reported were infusion site pain and infusion site reaction (redness and swelling). These symptoms were often severe and sometimes required treatment with narcotics or discontinuation of Remodulin. The IV infusion of Remodulin has been associated with a risk of blood stream infections, arm swelling, paresthesias, hematoma, and pain. Other common adverse events (≥3% more than placebo) seen with either SC or IV Remodulin were headache, diarrhea, nausea, jaw pain, vasodilatation, and edema

Indication

Remodulin is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise. Studies establishing effectiveness included patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (58%), PAH associated with congenital systemic-to-pulmonary shunts (23%), or PAH associated with connective tissue diseases (19%). It may be administered as a continuous subcutaneous infusion or continuous intravenous infusion; however, because of the risks associated with chronic indwelling central venous catheters, including serious blood stream infections, continuous intravenous infusion should be reserved for patients who are intolerant of the subcutaneous route or in whom these risks are considered warranted.

In patients with PAH requiring transition from Flolan® (epoprostenol sodium), Remodulin is indicated to diminish the rate of clinical deterioration. The risks and benefits of each drug should be carefully considered prior to transition.

Important SafetyInformation for Orenitram

Important Safety Information for Orenitram

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

Abrupt discontinuation or sudden large reductions in dosage of Orenitram may result in worsening of PAH symptoms

Orenitram inhibits platelet aggregation and increases the risk of bleeding

The Orenitram tablet shell does not dissolve. In patients with diverticulosis, Orenitram tablets can lodge in a diverticulum

DRUG INTERACTIONS / SPECIFIC POPULATIONS

Concomitant administration of Orenitram with diuretics, antihypertensive agents, or other vasodilators increases the risk of symptomatic hypotension

Orenitram inhibits platelet aggregation; there is an increased risk of bleeding, particularly among patients receiving anticoagulants

Co-administration of Orenitram and the CYP2C8 enzyme inhibitor gemfibrozil increases exposure to treprostinil; therefore, Orenitram dosage reduction may be necessary in these patients

Pregnancy Category C. Animal reproductive studies with Orenitram have shown an adverse effect on the fetus. There are no adequate and well-controlled studies in humans

It is not known whether treprostinil is excreted in human milk or absorbed systemically after ingestion. Because many drugs are excreted in human milk, choose Orenitram or breastfeeding

Safety and effectiveness in patients under 18 years of age have not been established

There is a marked increase in the systemic exposure to treprostinil in hepatically impaired patients

ADVERSE REACTIONS

In the 12-week placebo-controlled monotherapy study, adverse reactions that occurred at rates at least 5% higher on Orenitram than on placebo included headache, diarrhea, nausea, flushing, pain in jaw, pain in extremity, hypokalemia, and abdominal discomfort

Indication

Orenitram is a prostacyclin vasodilator indicated for treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity.

The study that established effectiveness included predominately patients with WHO functional class II-III symptoms and etiologies of idiopathic or heritable PAH (75%) or PAH associated with connective tissue disease (19%). When used as the sole vasodilator, the effect of Orenitram on exercise is about 10% of the deficit, and the effect, if any, on a background of another vasodilator is probably less than this.

Important Safety Information for Remodulin

WARNINGS AND PRECAUTIONS

Chronic intravenous (IV) infusions of Remodulin are delivered using an indwelling central venous catheter. This route is associated with the risk of blood stream infections (BSI) and sepsis, which may be fatal. Therefore, continuous subcutaneous (SC) infusion is the preferred mode of administration

Avoid abrupt withdrawal or sudden large reductions in dosage of Remodulin, which may result in worsening of PAH symptoms

Titrate slowly in patients with hepatic or renal insufficiency because such patients will likely be exposed to greater systemic concentrations relative to patients with normal hepatic or renal function

Remodulin dosage adjustment may be necessary if inhibitors or inducers of CYP2C8 are added or withdrawn. Co-administration of Remodulin with a CYP2C8 inhibitor increases exposure to treprostinil, or with an inducer, decreases exposure to treprostinil

DRUG INTERACTIONS/SPECIFIC POPULATIONS

Remodulin is a potent pulmonary and systemic vasodilator. Concomitant administration of Remodulin with blood pressure lowering agents, such as diuretics, antihypertensive agents, or other vasodilators, may increase the risk of symptomatic hypotension

Since Remodulin inhibits platelet aggregation, there may be an increased risk of bleeding, particularly among patients receiving anticoagulants

Safety and effectiveness of Remodulin in pediatric patients have not been established. It is unknown if geriatric patients respond differently than younger patients. Caution should be used when selecting a dose for geriatric patients

There are no adequate and well-controlled studies with Remodulin in pregnant women. It is not known whether treprostinil is excreted in human milk

ADVERSE REACTIONS

In clinical studies of SC Remodulin infusion, the most common adverse events reported were infusion site pain and infusion site reaction (redness and swelling). These symptoms were often severe and sometimes required treatment with narcotics or discontinuation of Remodulin. The IV infusion of Remodulin has been associated with a risk of blood stream infections, arm swelling, paresthesias, hematoma, and pain. Other common adverse events (≥3% more than placebo) seen with either SC or IV Remodulin were headache, diarrhea, nausea, jaw pain, vasodilatation, and edema

Indication

Remodulin is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise. Studies establishing effectiveness included patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (58%), PAH associated with congenital systemic-to-pulmonary shunts (23%), or PAH associated with connective tissue diseases (19%). It may be administered as a continuous subcutaneous infusion or continuous intravenous infusion; however, because of the risks associated with chronic indwelling central venous catheters, including serious blood stream infections, continuous intravenous infusion should be reserved for patients who are intolerant of the subcutaneous route or in whom these risks are considered warranted.

In patients with PAH requiring transition from Flolan® (epoprostenol sodium), Remodulin is indicated to diminish the rate of clinical deterioration. The risks and benefits of each drug should be carefully considered prior to transition.